Östrogen stimuliert das Homing endothelialer Progenitorzellen in Endometrioseherden
Östrogen stimuliert das Homing endothelialer Progenitorzellen in Endometrioseherden
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雌激素刺激子宫内膜异位病灶中内皮祖细胞的归巢
DOI：
10.1055/s-0035-1558352
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发表时间：
2015
影响因子：
2.7
通讯作者：
Laschke MW
中科院分区：
文献类型：
--
作者：
Rudzitis-Auth J;Nenicu A;Nickels RM;Menger MD;Laschke MW
内皮祖细胞（EPCs）进入微血管有助于血管病变的血管化。在此，我们分析了这一血管发生过程是否受雌激素的调节。分析雌激素和溶剂处理的人EPCs的迁移和管形成。在辐照的FVB/N小鼠中诱导子宫内膜异位病变，所述小鼠用来自FVB/N-TgN（Tie 2/绿色荧光蛋白）287 Sato小鼠的骨髓重建。在7天和28天内，动物接受100 μg/kg β-雌二醇17-戊酸酯或溶剂（对照）给药。通过高分辨率超声、卡尺测量、组织学和免疫组织化学分析病变生长、囊肿形成、绿色荧光蛋白+/Tie 2 +EPCs归巢、血管形成、细胞增殖和凋亡。流式细胞仪检测血循环EPCs的数量，体外实验表明，雌激素处理的EPCs具有更高的迁移和管形成能力，体内实验表明，循环EPCs的数量不受雌激素的影响。然而，雌激素显着增加了EPCs的数量纳入病变的微血管，导致改善早期血管化。雌激素进一步刺激病变的生长，表现为腺体大量扩张，基质层变平。这主要是因为腺体分泌活动增加，而细胞增殖和凋亡没有受到明显影响。这些发现表明子宫内膜异位症病变的血管生成依赖于雌激素，这为子宫内膜异位症复杂的病理生理学增加了一种新的子宫调节机制。
The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein+/Tie2+EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry.In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls.In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis.